Abstract summary 

Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.

Authors & Co-authors:  Nongmaithem Suraj S SS Beaumont Robin N RN Dedaniya Akshay A Wood Andrew R AR Ogunkolade Babatunji-William BW Hassan Zahid Z Krishnaveni Ghattu V GV Kumaran Kalyanaraman K Potdar Ramesh D RD Sahariah Sirazul A SA Krishna Murali M Di Gravio Chiara C Mali Inder D ID Sankareswaran Alagu A Hussain Akhtar A Bhowmik Biswajit W BW Khan Abdul Kalam A AKA Knight Bridget A BA Frayling Timothy M TM Finer Sarah S Fall Caroline H D CHD Yajnik Chittaranjan S CS Freathy Rachel M RM Hitman Graham A GA Chandak Giriraj R GR

Study Outcome 

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